The resistance of bacterial biofilms to physical and chemical agents is attributed in the literature to various interconnected processes. The limitation of mass transfer alters the growth rate, and physiological changes in the bacteria in the film also appear. The present work describes an approach to determination of the mechanisms involved in the resistance of bacteria to quaternary ammonium compounds (benzalkonium chloride) according to the C-chain lengths of those compounds. For Pseudomonas aeruginosa CIP A 22, the level of resistance of the bacteria in the biofilm relative to that of planktonic bacteria increased with the C-chain length. For cells within the biofilm, the exopolysaccharide induced a characteristic increase in surface hydrophilicity. However, this hydrophilicity was eliminated by simple resuspension and washing. The sensitivity to quaternary ammonium compounds was restored to over 90%. Staphylococcus aureus CIP 53 154 had a very high level of resistance when it was in the biofilm form. A characteristic of bacteria from the biofilm was a reduction in the percent hydrophobicity, but the essential point is that this hydrophobicity was retained after the biofilm bacteria were resuspended and washed. The recovery of sensitivity was thus only partial. These results indicate that the factors involved in biofilm resistance to quaternary ammonium compounds vary according to the bacterial modifications induced by the formation of a biofilm. In the case of P. aeruginosa, we have underlined the involvement of the exopolysaccharide and particularly the three-dimensional structure (water channels). In the case of S. aureus, the role of the three-dimensional structure is limited and drastic physiological changes in the biofilm cells are more highly implicated in resistance.

Metabolic and innate immune cues merge into a specific inflammatory response via unfolded protein response (UPR). Cell, Elsevier, In press, 177 (5), pp. SummaryInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC) are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.